ATP requirements for growth reveal the bioenergetic impact of mitochondrial symbiosis (2503.16962v1)

Abstract: Studies by microbiologists from the 1970s provided robust estimates for the energy supply and demand of a prokaryotic cell. The amount of ATP needed to support growth was calculated from the chemical composition of the cell and known enzymatic pathways that synthesize its constituents from known substrates in culture. Starting in 2015, geneticists and evolutionary biologists began investigating the bioenergetic role of mitochondria at eukaryote origin and energy in metazoan evolution using their own, widely trusted but hitherto unvetted model for the costs of growth in terms of ATP per cell. The more recent model contains, however, a severe and previously unrecognized error that systematically overestimates the ATP cost of amino acid synthesis up to 200 fold. The error applies to all organisms studied by such models and leads to conspicuously false inferences, for example that the synthesis of an average amino acid in humans requires 30 ATP, which no biochemistry textbook will confirm. Their ATP cost calculations would require that Escherichia coli obtains roughly 100 ATP per glucose and that mammals obtain roughly 240 ATP per glucose, propositions that invalidate evolutionary inferences so based. By contrast, established methods for estimating the ATP cost of microbial growth show that the first mitochondrial endosymbionts could have easily doubled the hosts available ATP pool, provided that genes for growth on environmental amino acids were transferred from the mitochondrial symbiont to the archaeal host and that the host for mitochondrial origin was an autotroph using the acetyl-CoA pathway.